Journal
TUMOR BIOLOGY
Volume 37, Issue 2, Pages 2425-2433Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-3966-1
Keywords
NPC; CDK4; miR-16; c-Myc; Feedback loop
Categories
Funding
- National Nature Science Fund of China [30971438, 81102061]
- New Star Plan of Pearl River Science and Technology from Guangzhou City [2011J2200009]
- Guangdong Science and Technology Planning Project [2014A020212342]
- Yangcheng Scholar Research Projects from Universities of Guangzhou [12A011D]
- Oustanding Young Teacher Training Project of Collegues and Universities in GuangDong Province [Yp2013136]
- Guangzhou Science and Technology Planning Project [2013J4100035]
- Ph.D. Programs Foundation of Ministry of Education of China [20134423110001]
Ask authors/readers for more resources
Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a negative automodulatory feedback loop between CDK4 and miR-16 that regulates cell cycle progression in nasopharyngeal carcinoma (NPC). By miRNA array and real-time PCR, we identified upregulation of tumor suppressor miR-16a, which inhibited cell cycle progression and sensitized NPC cells to chemotherapy. CDK4 knockdown reduced the expression of c-Myc, the latter of which directly suppresses the miR-16 expression by directly binding to the miR-16 promoter. Moreover, we found that miR-16 upregulation could reduce CDK4 expression by repressing CCND1 and thus forms a feedback loop via the CDK4/c-Myc/miR-16/CCND1 pathway. Finally, miR-16 was negatively correlated with CDK4 expression in NPC biopsies. In summary, our results define a double-negative feedback loop involving CDK4 and miR-16 mediated by c-Myc that modulates NPC cell growth and chemotherapy sensitivity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available